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We examined the role of NFkappaB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFkappaB1 (Nfkappab1-/-) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity ofNfkappab1-/-Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in theNfkappab1-/-mice. Bone marrow chimeric mice revealed that the Fo B cell-intrinsic loss of NFkappaB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes the differentiation of Fo helper CD4+T cells and acts in an autocrine manner to reduce antigen receptor and toll-like receptor activation thresholds in a population of proliferating IgM+Nfkappab1-/-Fo B cells. We demonstrate that p50-NFkappaB1 repressesIl-6transcription in Fo B cells, with the loss of NFkappaB1 also resulting in the uncontrolled RELA-driven transcription ofIl-6.Collectively, our findings identify a previously unrecognized role for NFkappaB1 in preventing multiorgan autoimmunity through its negative regulation ofIl-6gene expression in Fo B cells.